WO2012000529A1

WO2012000529A1 - Process for preparing magnetite or maghemite nanoparticles with controlled size using mild conditions

Info

Publication number: WO2012000529A1
Application number: PCT/EP2010/003983
Authority: WO
Inventors: Jens Baumgartner; Damien Faivre
Original assignee: Max-Planck-Gesellschaft zur Förderung der Wissenschaften e. V.
Priority date: 2010-07-01
Filing date: 2010-07-01
Publication date: 2012-01-05

Abstract

The invention relates to an improved process for preparing magnetite or maghemite nanoparticles with controlled size using mild conditions. The process according to the invention comprises coprecipitation of Fe²⁺ and Fe³⁺ ions in an aqueous solution under mild alkaline conditions in a pH range from 8 to 12 and a temperature from 15 to 40°C. In a more specific embodiment of the process according to the present invention, the coprecipitation is effected by providing an aqueous reaction medium comprising deionized water set to the desired pH and continuously adding a mixed aqueous solution of Fe²⁺ and Fe³⁺ salts to the reaction medium.

Description

Process for preparing magnetite or maghemite nanoparticles with controlled size

using mild conditions

Background of the Invention

Magnetic nanoparticles are of great interest for various bio- and nanotechnological applications, such as ferrofluids, magnetic pigments, contrast agents for magnetic resonance imaging (MRI), drug delivery carriers, hyperthermia cancer treatment, sensors and others

(Corchero and Villaverde, 2009; Lu et al., 2007). The iron oxide magnetite Fe₃0₄ is the preferred material for the aforementioned applications as it is easily accessible, its magnetic properties can be tuned with particle size and it is biocompatible. Typically, the smallest particles exhibit superparamagnetic behaviour meaning that their magnetization can reverse spontaneously under thermal influence. For magnetite nanoparticles the superparamagnetic size threshold varies between 25-30 nm

(Muxworthy and Williams, 2006; Muxworthy and Williams, 2009) . Above this size, the particles have a single magnetic domain and thus show maximum remanence and coercivity. Above the critical size of roughly 100 nm

(Muxworthy and Williams, 2006; Muxworthy and Williams, 2009) , particles form multiple domains to minimize their magnetostatic energy. This again leads to a decrease in remanence and coercivity.

Numerous methods have been developed for the synthesis of magnetite, including coprecipitation, thermolysis, sol-gel reactions and others (Laurent et al., 2008). The simplest and most widely used synthesis method is the coprecipitation of ferrous and ferric iron in aqueous solution as firstly described by Massart (Massart, 1981) . With this method, the nanoparticle size can be tuned between 2 and 12 nm by adjusting pH and ionic strength (Vayssieres et al., 1998). Thus, only superparamagnetic particles can be obtained this way. However, various applications specifically require particles with single domain properties for highest possible remanence and coercivity that unfortunately have remained hardly accessible by such simple synthetic routes. All the present methods producing larger particles indeed make use of high temperatures and/or pressures and/or precursors that have to be solubilized in organic solvents (WO 2006/001018 A2; Kim et al., 2009; Sugimoto and Matijevic, 1980) . This is clearly unfavourable with respect to particle yield as compared to the Massart technique. Furthermore, these conditions are environmentally and economically disadvantageous.

In view of this prior art, a main object of the present invention was to provide an improved method for preparing magnetite or maghemite nanoparticles , in particular single domain nanoparticles, with controlled size in a convenient, cost-efficient and environmentally friendly manner .

Said object was achieved by providing the process of present claim 1. Specific and/or preferred embodiments of the invention are the subject of further claims.

Description of the invention The inventive process involves the simple coprecipitation of ferrous and ferric iron in aqueous solution in mild pH. Said process enables the control of particle size from the superparamagnetic to the single domain and possibly multidomain size ranges as shown by transmission electron microscopy (TEM) , X-ray diffraction (XRD) and confirmed by magnetic measurements. The disclosed process which in particular allows producing single domain nanoparticles under soft chemical and physical conditions represents a great step forward for the development of applications based on single-domain magnetic particles.

The inventive process according to claim 1 comprises coprecipitation of Fe²⁺ and Fe³⁺ ions in an aqueous solution under mild alkaline conditions in a pH range from 8 to 12 and a temperature from 15 to 40°C.

In a more specific embodiment of the invention, the pH is in a range from 8 to 10, and preferably in a range from pH 8.5 to 9.5.

In another specific embodiment, the temperature is in a range from 20 to 30°C, more specifically from 22 to 28°C, preferably 24-26°C, in particular about 25°C.

Typically, the nanoparticles obtained in the process of the invention have diameters in a range from 10 to 100 nm, preferably from larger than 15 nm to 100 nm.

In an especially preferred embodiment, the nanoparticles are single domain nanoparticles having a diameter in a range from 20 nm to 60 nm.

In a preferred embodiment of the process according to the present invention, the coprecipitation is effected by providing an aqueous reaction medium comprising deionized water set to the desired pH and continuously adding a mixed aqueous solution of Fe²⁺ and Fe³⁺ salts to the reaction medium.

The reaction medium may be set to the desired pH by any suitable organic or inorganic base. Preferably the base is NaOH or KOH. Typically, the desired pH will be initially set before adding any iron ion solution and subsequently monitored and re-adjusted to the desired pH by adding further base if necessary.

The Fe²⁺ and Fe³⁺ salts are preferably inorganic salts, in particular selected from the group of FeCl₂ and FeCl₃, other halides of Fe²⁺/Fe³⁺, nitrates or sulfates of Fe²⁺/Fe³⁺.

According to a more specific embodiment of said process, in said mixed aqueous solution of Fe²⁺ and Fe³⁺ salts the Fe²⁺ and Fe³⁺ ions are present in a concentration of from 0.1 mol to 2 mol, preferably 0.1 to 1.5 mol, and in a Fe²⁺/Fe³⁺ ratio of about 2:5 to 3:5, preferably about 1:2.

Preferably, the mixed aqueous solution of Fe²⁺ and Fe³⁺ salts is added with at a rate of 0.1-0.001 vol . % of the initial reaction volume per minute.

Typically, the mixed aqueous solution of Fe²⁺ and Fe³⁺ salts is added during a time period of from 1 min to 24 h, more specifically during a time period of from 1 h to 15 h, such as from 2 h to 10 h or from 3 h to 6 h. It will be evident for the skilled artisan that the time period can be optimized for any desired nanoparticle size by routine experiments based on the technical teachings of the present application.

In a specific embodiment of the inventive process, the mixed aqueous solution of Fe²⁺ and Fe³⁺ salts is added during a time period of from 3 to 6 h, preferably from 4 to 5 h, and the prepared magnetite nanoparticles have diameters in the range from 25-30 nm.

Typically, the reaction conditions are set to provide an average growth rate of the initial magnetite particles of about 2-5, preferably 3-4, nm per hour.

Usually, the inventive process will be implemented in a non-oxidizing atmosphere, such as nitrogen or a noble gas. Preferably all media and solutions used are essentially free of oxygen, e.g. effected by purging with nitrogen or another inert gas.

Advantageously, the inventive process can be implemented at normal pressure of about 1 bar.

In one specific embodiment of the invention, the magnetite particles produced are further oxidized to maghemite particles, e.g. by exposition to an oxidating agent such as oxygen. Alternatively, if the coprecipi- tation is implemented in the presence of air oxygen, maghemite particles are formed initially. In the latter case, however, it is difficult to obtain larger particles than about 20 nm size.

The invention is further illustrated by the following non- limiting Examples and Figures. FIGURES

Fig. 1. Transmission electron micrographs (TEM) of growing magnetite particles after (a) 10 min, (b) 300 min and (c) 600 min. Scale bar represents 100 nm.

Fig. 2. Synchrotron X-ray diffractogramm obtained from magnetite nanoparticles after 600 min growth.

Fig. 3. Development of the mean particle size over growth time. Sampling of 3 independent reactions with a 1 M iron solution. Error bars represent standard deviation.

Fig. 4. magnetic measurements at 300 K obtained after 5, 60 and 480 min reaction time. The increasing domain size increases remanence and coercitivity of the samples.

EXAMPLE 1

synthesis of magnetite nanoparticles

Magnetite nanoparticles with controlled size were synthesized using a modified version of the Massart route, Briefly, instead of fast addition of an iron solution to a strong base, iron was slowly added to a reactor with mild alkaline conditions.

In particular, magnetite nanoparticles were prepared by coprecipitation of FeCl₂ and FeCl₃ in a reactor maintained at 25 ± 0.1 °C by a water bath under constant pH conditions and nitrogen atmosphere. Deionized water and all solutions were initially purged with nitrogen before use .

10 mL deionized water was set to pH 9 with 1 M NaOH and equilibrated to 25 ± 0.1 °C. A I M iron solution consisting of 0.33 M FeCl₂ and 0.67 M FeCl₃ was added at a rate of 1 μΐ x min^"1 using a Metrohm 776 Dosimat^® pump. The pH was kept constant at pH = 9.0 ± 0.4 by addition of a 1 M NaOH solution controlled by a Metrohm 719 Titrino^® titration device coupled to a pH electrode (Metrohm Biotrode^®) . To study the evolution of nanoparticles, 60 μΐ samples were taken at given times after the addition of the iron solution started and were analyzed by TEM and XRD. For magnetic measurements, the final precipitate was separated by centrifugation, washed with deionized water and freeze-dried.

EXAMPLE 2

characterization of magnetite nanoparticles

TEM. Transmission electron micrographs were acquired on a Zeiss EM Omega 912X at an acceleration voltage of 120 kV. Samples were prepared by dropping the respective solution on a carbon-coated copper grid.

XRD. Wide angle X-ray powder diffraction was performed at the μ-spot beamline of the BESSY synchrotron radiation facility (Berlin, Germany) , with an energy of 15 keV (λ = 0.82656285 A), a beam size of 100 pm and a Si 311 monochromator to reduce the beam divergence. Particle sizes were estimated by using the Scherrer equation, considering a correction for the instrumental peak broadening (Paris et al., 2007).

SQUID. Measurements were performed on a MPMS at 300K.

The nanoparticles initially formed in Example 1 were made of magnetite as confirmed by XRD and lie within the superparamagnetic size range, with mean particle dimensions of 15 nm as evidenced by TEM after 10 min reaction time (Fig. la) . Particles of this size range are typically produced in coprecipitation syntheses when either titrating a respective iron solution to alkaline pH or addition of the iron solution to an alkaline reservoir (Berger et al., 1999; Massart, 1981). It has been reported that particle size can be tailored within 2 to roughly 12 nm by adjusting pH and ionic strength during synthesis (Vayssieres et al., 1998). However, with the present method, it is possible to obtain much larger particles that are not reported in the literature using such simple set-ups. In experiments of the inventors, the magnetite particles were able to grow with time. Figs, lb and lc show magnetite particles obtained according to Example 1 after reaction times of 300 and 600 min, respectively. As can be seen in the latter micrograph, single magnetite crystals can reach sizes over 100 nm after growth.

To study the mean size of crystals in the bulk, the domain size was analyzed by wide angle X-ray diffraction (Fig. 2) and Scherrer analysis based on broadening of the most prominent (311) peak. As evident from Fig. 3, continuous addition of iron to the reaction medium according to Example 1 resulted in near-linear crystal growth at an average rate of 3.5 nm per hour. Magnetite nanoparticles become magnetically remanent at room temperature at a size of around 25-30 nm. Thus, after a growth time of around 4-5 hours single domain particles can be obtained with this method.

To investigate whether the increasing crystallite size does indeed change their magnetic properties, SQUID measurements were performed on samples taken after several time points (Table 1) .

Table 1

Synthesis Mean particle Coercivity (Oe)

time (min) size (nm)

15 17 12

60 18 45

240 28 115

480 43 106

As can be seen in Fig. 4, initially formed particles show no hysteresis at room temperature in accordance with their superparamagnetic behaviour. With time, growing crystallites show increasing remanence and coercivity due to their increasing domain size. The coercivity H_c at 300 K increases over time from initially almost zero to 115 Oe after 240 min. After 480 min the coercivity reduces slightly to 106 Oe indicating the possible presence of multidomain particles. The critical size for multidomain magnetite particles is 128 nm, which is close to the size of single particles observed with TEM after 600 min (Kim et al., 2009). Consequently, the drop in coercivity might also indicate an earlier presence of such nanoparticles.

Summarizing, the present invention allows to produce nanoparticles of magnetite having a size from about 10 (superparamagnetic) to about 100 nm (limit between single to multi-domain) by simple coprecipitation of ferrous and ferric iron in mild alkaline conditions. With the presented method, particles grow from an initial superparamagnetic size of 10 to 15 nm by around 3 to 4 nm per hour on average. Thus, the magnetic domain size of magnetite nanoparticles can be precisely controlled from superparamagnetic to single domain size and possibly even beyond. The technique is environmentally and economically favourable when compared to existing techniques leading to such sizes as the reaction proceeds under soft chemical conditions. Reactions indeed run at room temperature, ambient pressure, at mild pH and without the use of any organic solvent.

This also opens up the possibility to produce particles in the presence of sensitive additives, such as biomolecules, e.g. proteins, peptids and nucleic acids, which are necessary for the aforementioned bionanotechnological applications .

References

Berger, P. et al., 1999. Preparation and properties of an aqueous ferrofluid. Journal of Chemical Education, 76(7): 943-948.

Corchero, J.L. and Villaverde, A., 2009. Biomedical applications of distally controlled magnetic nanoparticles. Trends Biotechnol., 27(8): 468-476.

Kim, D. et al., 2009. Synthesis of Uniform Ferrimagnetic Magnetite Nanocubes. J. Am. Chem. Soc, 131(2): 454-455.

Laurent, S. et al., 2008. Magnetic Iron Oxide Nanoparticles: Synthesis, Stabilization, Vectorization, Physicochemical Characterizations, and Biological Applications. Chem. Rev., 108(6): 2064-2110.

Lu, A.-H., Salabas, E.L. and Schiith, F. , 2007. Magnetic Nanoparticles: Synthesis, Protection, Functionalization, and Application. Angew. Chem. Int. Ed., 46(8): 1222-1244. Massart, R., 1981. Preparation of aqueous magnetic liquids in alkaline and acidic media. Magnetics, IEEE Transactions on, 17 (2) : 1247-1248.

Muxworthy, A.R. and Williams, W. , 2006. Critical single- domain/multidomain grain sizes in non-interacting and interacting elongated magnetite particles: Implications for magnetosomes . J. Geophys . Res., Ill: B12S12.

Muxworthy, A.R. and Williams, W. , 2009. Critical superparamagnetic/single-domain grain sizes in interacting magnetite particles: implications for magnetosome crystals. J. R. Soc. Interf., 6(41): 1207-1212.

Paris, O. et al., 2007. A new experimental station for simultaneous X-ray microbeam scanning for small- and wide- angle scattering and fluorescence at BESSY II. J. Appl . Cryst., 40:S466-S470.

Sugimoto, T. and Matijevic, E . , 1980. Formation of Uniform Spherical Magnetite Particles by Crystallization from Ferrous Hydroxide Gels. J. Col. Interf. Sci., 74(1): 227- 243.

Vayssieres, L., Chaneac, C, Tronc, E. and Jolivet, J. P., 1998. Size Tailoring or Magnetite Particles Formed by Aqueous Precipitation: An Example of thermodynamic Stability of Nanometric Oxide Particles. J. Col. Interf. Sci., 205: 205-212.

Claims

1. A process for preparing magnetite or maghemite nanoparticles with controlled size comprising coprecipitation of Fe²⁺ and Fe³⁺ ions in an aqueous solution under mild alkaline conditions in a pH range from 8 to 12 and a temperature from 15 to 40°C.

2. The process according to claim 1, wherein the nanoparticles have diameters in a range from 10 to 100 nm, preferably from larger than 15 nm to 100 nm.

3. The process according to claim 2, wherein the nanoparticles are single domain nanoparticles having a diameter in a range from 20 nm to 60 nm.

4. The process according to any one of claims 1-3, wherein the pH is in a range from 8.5 to 9.5.

5. The process according to any one of claims 1-4, wherein the temperature is in a range from 22 to 28 °C, preferably 24-26°C.

6. The process according to any one of claims 1-5, wherein the coprecipitation is effected by providing an aqueous reaction medium comprising deionized water set to the desired pH and continuously adding a mixed aqueous solution of Fe²⁺ and Fe³⁺ salts to the reaction medium.

7. The process according to claim 6, wherein the Fe²⁺ and Fe³⁺ salts are inorganic salts, in particular selected from the group of FeCl₂ and FeCl₃, other halides of Fe²⁺/Fe³⁺, nitrates or sulfates of Fe²⁺/Fe³⁺.

8. The process according to claim 6 or 7, wherein in said mixed aqueous solution of Fe²⁺ and Fe³⁺ salts the Fe²⁺ and Fe³⁺ ions are present in a concentration of from 0.1 mol to 2 mol and in a Fe²⁺/Fe³⁺ ratio of 2:5 to 3:5, preferably about 1:2.

9. The process according to any one of claims 6-8, wherein the mixed aqueous solution of Fe²⁺ and Fe³⁺ salts is added with at a rate of 0.1-0.001 vol.% of the initial reaction volume per minute.

10. The process according to any one of claims 6-9, wherein the mixed aqueous solution of Fe²⁺ and Fe³⁺ salts is added during a time period of from 1 min to 24 h.

11. The process according to claim 10, wherein the mixed aqueous solution of Fe²⁺ and Fe³⁺ salts is added during a time period of from 4 to 5 h and the prepared magnetite nanoparticles have diameters in the range from 25-30 nm.

12. The process according to any one of claims 1-11, wherein the reaction conditions are set to provide an average growth rate of the initial magnetite particles of about 2-5, preferably 3-4, nm per hour.

13. The process according to any one of claims 1-12, which is implemented in a non-oxidizing atmosphere.

14. The process according to any one of claims 1-13, which is implemented in the presence of biomolecules.

15. The process according to any one of claims 1-14, wherein the magnetite particles produced are further oxidized to maghemite particles.